Epigenetics changes caused by the fusion of human embryonic stem cell and ovarian cancer cells

Abstract

To observe the effect of gene expression and tumorigenicity in hybrid cells of human embryonic stem cells (hESCs) and ovarian cancer cells in vitro and in vivo using a mouse model, and to determine its feasibility in reprogramming tumour cells growth and apoptosis, for a potential exploration of the role of hESCs and tumour cells fusion in the management of ovarian cancer. Stable transgenic hESCs (H1) and ovarian cancer cell line OVCAR-3 were established before fusion, and cell fusion system was established to analyse the related indicators. PTEN expression in HO-H1 cells was higher than those in the parental stem cells and lower than those in parental tumour cells; the growth of OV-H1 (RFP+GFP) hybrid cells with double fluorescence expressions were obviously slower than that of human embryonic stem cells and OVCAR-3 ovarian cancer cells. The apoptosis signal of the OV-H1 hybrid cells was significantly higher than that of the hESCs and OVCAR-3 ovarian cancer cells. In vivo results showed that compared with 7 days, 28 days and 35 days after inoculation of OV-H1 hybrid cells; also, apoptotic cell detection indicated that much stronger apoptotic signal was found in OV-H1 hybrid cells inoculated mouse. The hESCs can inhibit the growth of OVCAR-3 cells in vitro by suppressing p53 and PTEN expression to suppress the growth of tumour that may be achieved by inducing apoptosis of OVCAR-3 cells. The change of epigenetics after fusion of ovarian cancer cells and hESCs may become a novel direction for treatment of ovarian cancer.

Therapeutic role of PTEN in tissue regeneration for management of neurological disorders: stem cell behaviors to an in-depth review

“…Considering that aggressive tumor cells have similar proliferation and plasticity properties to ESCs, PTEN regulation in the ESC microenvironment instead of the tumor microenvironment (TME) represents an ideal intervention to prevent early-stage tumorigenesis [ 10 ]. In addition, enhanced expressions of P53 and PTEN promote the expression levels of caspase 9 in human ESCs, but inhibit AKT phosphorylation and tumor growth, demonstrating that the PTEN-P53 signaling pathway governs cell cycle exit in tumors [ 11 ]. As a typical tumor suppressor gene, loss-of-function in PTEN can result in a deficiency of tumor suppressor signaling in the downstream cascades, providing a favorable environment for tumor growth.…”

Cell‑cell fusion as an important mechanism of tumor metastasis (Review)

“…However, it is not always the case that fusion cells will exhibit increased tumorigenicity or TSC-like properties. He et al (51) reported in 2017 that hESCs and ovarian cancer cells can fuse in vitro spontaneously, and the fused cells interestingly exhibited epigenetic changes that led to inhibition of growth, which may provide a novel direction for the treatment of ovarian cancer. Although cell fusion between BMDCs and somatic cells may be the origin of TSCs, the hybrid cells that form as a result of the fusion of human HSCs and esophageal carcinoma cells did not generate esophageal TSCs (52,53).…”